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Year : 2015  |  Volume : 29  |  Issue : 3  |  Page : 145-149

A comparative study of Intrathecal clonidine and fentanyl along with bupivacaine in spinal anesthesia for caesarean section

Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India

Date of Web Publication1-Dec-2015

Correspondence Address:
Nongthombam Ratan Singh
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal - 795 004, Manipur
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0972-4958.170782

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Background: Patients undergoing caesarean section under spinal anaesthesia often experience pain in the perioperative period. The aim of this study was to evaluate the effect of intrathecal combination of clonidine and bupivacaine compared with bupivacaine and opioid on the incidence and severity of pain in elective caesarean section cases. Materials and Methods: Ninety healthy parturient at term scheduled for elective caesarean delivery were randomly allocated to receive intrathecally hyperbaric bupivacaine alone (Group B) or combined with 75 μg of clonidine (Group C) or with fentanyl 25 μg (Group F). The peak sensory block level, time to reach peak block level from injection, time to two segment regression, maximum degree of motor block, side effects, perioperative analgesic requirements and time to the first analgesic request after surgery were recorded and statistically analysed. Results: Time to two segment regression was significantly prolonged in Group C (78.87 ± 13.362 mins.) and Group F (84.17 ± 12.463 mins.) as compared to Group B (69.70 ± 14.005 min); (P < 0.05). There was significant prolongation of postoperative analgesia as seen by the time to first analgesic request after surgery in Group C (3.550 ± 1.1013 hours) and Group F (5.183 ± 1.1706 hours) as compared to Group B (2.350 ± 0.9016 hours). (P < 0.05). There was increased incidence of hypotension and nausea in Group C compared to other two groups. Conclusion: Perioperative analgesia was prolonged by the addition of 75 μg of clonidine and 25 μg fentanyl to bupivacaine, with increased side effects of nausea, vomiting and hypotension in the clonidine group.

Keywords: Caesarean section, clonidine, fentanyl, Intrathecal, spinal anaesthesia

How to cite this article:
Bhattacharjee A, Singh NR, Singh SS, Debbrama B, Debbarma P, Singh TH. A comparative study of Intrathecal clonidine and fentanyl along with bupivacaine in spinal anesthesia for caesarean section. J Med Soc 2015;29:145-9

How to cite this URL:
Bhattacharjee A, Singh NR, Singh SS, Debbrama B, Debbarma P, Singh TH. A comparative study of Intrathecal clonidine and fentanyl along with bupivacaine in spinal anesthesia for caesarean section. J Med Soc [serial online] 2015 [cited 2021 Dec 8];29:145-9. Available from:

  Introduction Top

Spinal anaesthesia is often used for both elective and emergency caesarean section. However, one disadvantage of spinal anaesthesia with bupivacaine alone is its relatively short duration of action, and the need for early analgesic intervention in the post operative period. The concept of co-induction of anesthesia has come forward by administering short acting lipophilic opioids like fentanyl and a selective α2 agonist like clonidine so as to reduce the dose requirement of bupivacaine and its adverse effects and prolong analgesia in the post operative period. [1]

The clinical efficacy of intrathecal opioids to relieve visceral pain has also been demonstrated by several workers. [2],[3] The addition of fentanyl 10 μg to hyperbaric bupivacaine 10.5-12.5 mg increases the intraoperative and early postoperative quality of subarachnoid block. [2]

Fentanyl, a synthetic opioid and μ receptor agonist, is about 100 times more potent than morphine as an analgesic. It is most commonly administered intravenously, although it is also commonly administered epidurally and intrathecally for acute postoperative and chronic pain management. Since it is more lipid soluble than morphine, the risk of delayed respiratory depression due to rostral spread of intraspinally administered narcotic to respiratory centres is greatly reduced. [4]

Intrathecal α2 receptor agonists have been found to have antinociceptive action for both somatic and visceral pain. Clonidine is a selective partial agonist for α2-adrenoreceptors, with a ratio of approximately 200:1 (α2 to α1). Intrathecal clonidine increases the duration of sensory and motor spinal block when added to spinal local anaesthetics and this effect of clonidine is dose dependent and doses of more than 75 μg intrathecal clonidine is accompanied by excessive sedation, hypotension and bradycardia. [5]

So, this study was taken up to compare the effects of fentanyl or clonidine when given intrathecally along with bupivacaine as regards the incidence and severity of pain in elective caesarean section cases.

  Materials and Methods Top

Following institutional ethical committee approval and obtaining written informed consent 90 patients (ASA [6] I and II) of 18-45 yrs, undergoing elective caesarean section were recruited in this prospective randomized, double-blinded study. The study drug was prepared by an anaesthesiologist not involved in the study in a 5 ml syringe in equal volume.

Based on the previous study of Benhamou et al. [7] the sample size calculated for this study, assuming α value of 0.05 and β value of 0.2 {(power = 1- β) = 0.8(80%)}, is 28 in each group. Considering any dropouts, we had enrolled 30 patients in each group.

Using computer generated randomisation, the patients were allocated into three groups of thirty patients each in each groups (n = 30, in each group) namely:

  • Group B (control): Inj. Bupivacaine 0.5% (2 ml) + Normal saline 0.5 ml. (2.5 ml)
  • Group F (Fentanyl): Inj. Bupivacaine 0.5% (2 ml) + Fentanyl 0.5 ml (25 μg) (2.5 ml)
  • Group C (Clonidine): Inj. Bupivacaine 0.5% (2 ml) + Clonidine 0.5 ml (75 μg) (2.5 ml)

Patients with a history of back surgery, infection at injection site, coagulopathy, hypovolemia, increased intracranial pressure, indeterminate neurologic disease, spinal deformities, known hypersensitivity to local anaesthetics, opioids or clonidine was excluded from the study.

In the lateral decubitus position, under strict aseptic and antiseptic precautions, mid-line spinal puncture was performed at L3-L4 with a 25G Quincke needle and after free flow of CSF the drug was administered. The following parameters were observed viz. peak sensory block level, time to peak block level from injection, time to two segment regression, degree of motor block, side effects, perioperative analgesic requirements, time to the first analgesic request after surgery.

Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 21 for windows. The parameters recorded were entered in a computer and compared between the three groups using chi square test for categorical variables, ANOVA for continuous variables. A P-value of <0.05 was considered as statistically significant.

  Results Top

The demographic profile which included the patients' age, weight, height and ASA physical classification were similar and no significant difference (P > 0.05) was observed amongst the groups [Table 1].
Table 1: Demographic profile

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Peak sensory block level (PSBL) and time to reach peak sensory block (TPSBL) was similar in all the three groups with P value 0.093 and 0.087 respectively. The time taken for two segment regression (TTSR) in Group B was 69.70 ± 14.005 min., in group C it was 78.87 ± 13.362 min. and in group F it was 84.17 ± 12.463 min. and it was statistically significant (P = 0.000). The time for first analgesic request (TFAR) in Group B was 2.35 ± 0.9016 hours, in group C - 3.55 ± 1.1013 hours and in group F-5.183 ± 1.1706 hours which is significant statistically (P = 0.000). The overall quality of maximum motor blockade (MBS) was also similar in the three groups (P = 0.364) [Table 2]. These finding can be explained by the relatively high volume (2.5 ml) of drug used in all the three groups.
Table 2: Showing the characteristics of the spinal block in the groups.

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The mean time to reach T4-6(TT4-6) segment (Group B/Group C/ Group F = 8.10 ± 3.255/6.25 ± 2.137/6.46 ± 3.294 min.) was not statistically significant (P > 0.05) The incidence of side effects were different among the study drugs, with higher incidence of hypotension (19/30; P = 0.001), nausea (16/30; P = 0.000) in the clonidine group and pruritus was (7/30; P = 0.001) in fentanyl group [Table 3], which were statistically significant. The SBP showed a decrease in the first 8 min. in all the three groups and thereafter it was stabilised [Figure 1] but the changes were not significant when compared at the corresponding time intervals. No significant changes were observed in the pulse rate at the same time intervals in the three groups [Figure 1].
Figure 1: Showing the mean systolic blood pressure and mean pulse rate of the three groups at various time intervals

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Table 3: Adverse effects

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  Discussion Top

Clonidine, a selective partial agonist for α2 adrenoreceptors known to increase both sensory and motor block of local anaesthetics, after intrathecal administration exerts its analgesic effects through activation of post synaptic α2 receptors in substantia gelatinosa of spinal cord. [8],[9]

Fentanyl and bupivacaine co-administration has a synergistic inhibitory action on the Aδ and C- fiber conduction causing improved perioperative analgesia. [10]

Benhamou et al. [7] and several other workers [11],[12] used varying doses of intrathecal clonidine combined with varying doses of bupivacaine. Increment of spinal clonidine doses enhanced side effects like sedation, hypotension, longer sensory and motor blockade [12] whereas low doses have less postoperative analgesia. [13],[14]

On the other hand, in two studies very small doses of intrathecal clonidine (25 μg and 30-75 μg) [15],[16] increased the duration of the pain-free interval compared with only spinal local anaesthetics without causing any significant side effects. We were interested to test an intrathecal dose in the lower range as marked decrease in blood pressure is only observed with 150 μg dose of spinal clonidine and relative hemodynamic stability is maintained after larger doses (300-450 μg) but with marked sedation as observed by Filos et al. [12]

In our study there was no significant difference in peak sensory block level and time to reach peak sensory block level in all the three groups. These can be explained due to comparatively large volume of drug (2.5 ml) used in all the three groups in this study. The time to two segment regression (min) was significantly higher in bupivacaine+fentanyl group (84.17 ± 12.46 mins) and bupivacaine + clonidine group (78.87 ± 13.362 mins) than bupivacaine alone group (69.70 ± 14.005 mins). Singh et al. [3] reported two segment regression time of 90 min which also correlate with our study. These findings are comparable with Hunt et al. [2] and Sethi et al. [13]

Belzarena [17] observed that time to request of postoperative analgesic increased and total analgesia consumption decreased in a dose-dependent manner when intrathecal fentanyl was applied in doses of 0.25 μg/kg, 0.5 μg/kg, and 0.75 μg/kg. Thus, time to first postoperative analgesic request increased from 3 h with control to 11 h and 13 h with 0.5 μg/kg and 0.75 μg/kg fentanyl, respectively. Similarly in the present study, the time to first analgesic to request was also significantly longer in bupivacaine + fentanyl group (5.183 ± 1.1706 hours), and bupivacaine + clonidine group (3.550 ± 1.1013 hours) (P = 0.000).

Pruritus, a unique feature of intrathecal opioids and pruritus, but not nausea and vomiting, increased with increasing doses of fentanyl. [17] Singh et al. [3] demonstrated that fentanyl 25 μg reduced the analgesic requirement without increasing the incidence of episodes of desaturation, nausea, or pruritus during the early postoperative period. So, we decided to go with a dose of 25 μg to limit the side effects as well as to increase the postoperative analgesia and it was observed that 6 patients (8%) in group F developed pruritus. This result is almost comparable with Shawagfeh et al. [18] where he reported 6% incidence of pruritus with 25μg fentanyl and Al Ghanem [5] and Unal et al. [19] reported a high incidence of 13% and 42.6% to 50% respectively.

Benhamou et al. [7] demonstrated improved intraoperative spinal analgesia by adding 75 μg of clonidine to bupivacaine and the side effects were not increased with this dose. Lavand'homme et al. [20] showed higher incidence of hypotension and sedation in clonidine 150 μg group then in clonidine 75 μg. Hence, the dose of clonidine was limited to 75 μg in this study to decrease the side effects and to increase the postoperative analgesia.

Intrathecally, fentanyl exerts its effects by combining with opioid receptors in the dorsal horn of spinal cord and may have a supraspinal spread and action. Intrathecal fentanyl when added to spinal local anaesthetics reduces significant visceral and somatic pain and the analgesic effect has been proved by many studies. [2],[3]

In the present study, the duration of analgesia with 25 μg of intrathecal fentanyl was 5.183 ± 1.706 h. However, Hunt et al. [2] showed no further increase in duration of analgesia nor decrease in 24 h opioid requirements when the dose of intrathecal fentanyl was increased to 6.25 μg.

Sethi et al. [13] and Lavand'homme et al. [20] showed increased intraoperative hypotension in the clonidine group which may be favourably compared with the findings of the present study. However, the haemodynamics were much more stable with less amount of nausea in the fentanyl group in our study and was in accordance with study by Hunt et al. [2]

Limitations of the present study are:

  1. No preloading or co loading to ameliorate hypotension.
  2. Varied doses of the two studied drugs and local anaesthetic could have been used.

  Conclusion Top

It can be concluded from the present study that perioperative analgesia for caesarean section was prolonged by the addition of 75 μg of clonidine and 25 μg fentanyl to bupivacaine. However, prolongation of perioperative analgesia was more with fentanyl compared to clonidine, which also had unwanted side effects like nausea, vomiting and hypotension.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Ben-David B, Solomon E, Levin H, Admoni H, Goldik Z. Intrathecal fentanyl with small-dose dilutes bupivacaine: Better anesthesia without prolonging recovery. Anesth Analg 1997;85:560-5.  Back to cited text no. 1
Hunt CO, Naulty JS, Bader AM, Hauch MA, Vartikar JV, Datta S, et al. Perioperative analgesia with subarachnoid fentanyl-bupivacaine for cesarean delivery. Anesthesiology 1989;71:535-40.  Back to cited text no. 2
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Al-Ghanem SM, Massad IM, Al-Mustafa MM, Al-Zaben KR, Qudaisat IY, Qatawneh AM, et al. Effect of adding dexmedetomidine versus fentanyl to intrathecal bupivacaine on spinal block characteristics in gynaecological procedures: A double blind controlled study. Am J Applied Sci 2009;6:882-7.  Back to cited text no. 5
Fischer SP, Bader AM, Sweitzer B. Perioperative evaluation. In: Miller RD, editor. Miller's Anesthesia. 7 th ed. Philadelphia: Churchill Livingstone Elsevier; 2010. p.1002.  Back to cited text no. 6
Benhamou D, Thorin D, Brichant JF, Dailland P, Milon D, Schneider M. Intrathecal clonidine and fentanyl with hyperbaric bupivacaine improves analgesia during cesarean section. Anesth Analg 1998;87:609-13.  Back to cited text no. 7
Chiari A, Eisenach JC. Spinal anaesthesia: Mechanisms, agents, methods, and safety. Reg Anesth Pain Med 1998;23:357-62; discussion 384-7.  Back to cited text no. 8
Reddy SV, Yaksh TL. Spinal noradrenergic terminal system mediates antinociception. Brain Res 1980;189:391-401.   Back to cited text no. 9
Wang C, Chakrabarti Mk, Whitwam JG. Specific enhancement by fentanyl of the effects of intrathecal bupivacaine on nociceptive afferent but not on sympathetic efferent pathways in dogs. Anaesthesiology 1993;79:766-73; discussion 25A.  Back to cited text no. 10
Paech MJ, Timothy PJ, Orlikowski CE, Yeo ST, Banks SL, Evans SF, et al. Postcesarean analgesia with spinal morphine, clonidine, or their combination. Anesth Analg 2004;98:1460-6, table of contents.  Back to cited text no. 11
Filos KS, Goudas LC, Patroni O, Polyzou V. Intrathecal clonidine as a sole analgesic for pain relief after caesarean section. Anesthesiology 1992;77:267-74.  Back to cited text no. 12
Sethi BS, Samuel M, Sreevastava D. Efficacy of analgesic effects of low dose intrathecal clonidine as adjuvant to bupivacaine. Indian J Anaesth 2007;51:415-9.  Back to cited text no. 13
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Alahuhta S, Kangas-Saarela T, Hollmén AI, Edström HH. Visceral pain during caesarean section under spinal and epidural anaesthesia with bupivacaine. Acta Anaesthesiol Stand 1990;34:95-8.  Back to cited text no. 16
Belzarena SD. Clinical effects of intrathecally administered fentanyl in patients undergoing cesarean section. Anesth Analg 1992;74:653-7.  Back to cited text no. 17
Shawagfeh M, Sbaihat AS, Mayyas EA, Alomari AD, Fawaris SG. Low-dose Bupivacaine with fentanyl spinal anesthesia to prevent spinal-induced hypotension in adults. RMJ 2011;36:116-9.   Back to cited text no. 18
Unal D, Ozdogan L, Ornek HD, Sonmez HK, Ayderen T, Arslan M, et al. Selective spinal anaesthesia with low-dose bupivacaine and bupivacaine + fentanyl in ambulatory arthroscopic knee surgery. JPMA 2012;62:313.  Back to cited text no. 19
Lavand'homme PM, Roelants F, Waterloos H, Collet V, De Kock MF. An evaluation of the postoperative antihyperalgesic and analgesic effects of intrathecal clonidine administered during elective caesarean delivery. Anesth Analg 2008;107:948-55.  Back to cited text no. 20


  [Figure 1]

  [Table 1], [Table 2], [Table 3]

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